1.1. Metabolic Conditions
Obesity is a well-known risk factor for the development of many very common diseases such as atherosclerosis, hypertension, type 2 diabetes (non-insulin dependent diabetes mellitus (NIDDM)), dyslipidemia, coronary heart disease, and osteoarthritis and various malignancies. It also causes considerable problems through reduced motility and decreased quality of life. The incidence of obesity and thereby also these diseases is increasing throughout the entire industrialized world.
The term obesity implies an excess of adipose tissue. In this context obesity is best viewed as any degree of excess adiposity that imparts a health risk. The cut off between normal and obese individuals can only be approximated, but the health risk imparted by the obesity is probably a continuum with increasing adiposity.
Even mild obesity increases the risk for premature death and conditions such as diabetes, dyslipidemia, hypertension, atherosclerosis, gallbladder disease and certain types of cancer. In the industrialized western world the prevalence of obesity has increased significantly in the past few decades. Because of the high prevalence of obesity and its health consequences, its prevention and treatment should be a high public health priority.
When energy intake exceeds expenditure, the excess calories are stored predominately in adipose tissue, and if this net positive balance is prolonged, obesity results, i.e., there are two components to weight balance, and an abnormality on either side (intake or expenditure) can lead to obesity. This process may be counteracted by increasing the energy expenditure (for instance via exercise) or decreasing the energy intake (for instance by dieting). Except for exercise, diet and food restriction, which is not feasible for a vast number of subjects, no convincing treatment for reducing body weight effectively and acceptably currently exist.
One possible way to increase energy expenditure is by increasing the metabolic rate. Agents which act by increasing the metabolic rate may thus be useful for treating obesity, but also for treating other conditions such as atherosclerosis, hypertension, diabetes, especially type 2 diabetes (NIDDM (non-insulin dependent diabetes mellitus)), dyslipidemia, coronary heart disease, gallbladder disease, osteoarthritis and various types of cancer such as endometrial, breast, prostate and colon cancers and the risk for premature death.
Thus, it would be desirable to identify agents that can increase energy expenditure. Preferably, such agents would be natural agents that avoid side effects associated with pharmaceutical compounds.
1.2. Gut Biome
The infant gut is sterile before birth. After birth, the gut is rapidly colonized by environmental bacteria until a dense gut biome is established. Infants delivered vaginally acquire gut colonizing bacteria from their mother's vaginal and fecal flora. In contrast, infants delivered by cesarean section are not exposed to their mother's vaginal and fecal flora during birth and thus develop a gut biome that is different in composition than the gut biome of infants delivered vaginally. These differences in gut biome composition persist in the months immediately following birth. Likewise, differences in gut biome composition have been observed between infants that are breast fed and those that are formula fed.
The adult human gut has approximately 1013 (10,000,000,000,000) individual residents (Bäckhead, F., et al. (2004) PNAS Volume 101; no 44 pp. 15718-15723) and there are three consistent enterotypes established across many human cultural backgrounds (Arumugam, M. et al. (2011) Nature Vol. 473 pp. 174-180). The gut biome is influenced by plant based polyphenols in the diet and it is believed that the microbes convert them to be bioavailable to the human host (Rastmanesh, R. (2011), Chemico-Biol. Interact. Vol. 189 pp. 1-8; Moco, S., F. J. Martin, and S. Rezzi. (2012) J. Proteome Res. Volume 11, pp. 4781-4790). Acting as an organ, the gut biome is also responsible for conversion and production of key vitamins such as cholecalciferol (vitamin D25), biotin (vitamin H), riboflavin (vitamin B2), pantothenate (vitamin B5), ascorbate (vitamin C), thiamine (vitamin B1) and folate (vitamin B9); particularly in two (Bacteroides and Prevotella) of the three enterotypes (Bacteroides, Ruminococcus, and Prevotella) discovered. Some polyphenols have been described as vitamins in their own right by Dr. Norman Hollenberg, Professor of Medicine at Harvard Medical School. However, modern diets, particularly Western diets comprising high amounts of processed foods, may promote a gut biome composition that fails to convert or produce adequate or optimal amounts of these key vitamins.
Thus, it would be desirable to identify agents that can “fill in the nutritional gaps” caused by consumption of traditionally processed foods and modulate the human gut biome to achieve improved health. Preferably, such agents would be natural agents that avoid side effects associated with pharmaceutical compounds.